The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif.

BS69 is a transcriptional co-repressor protein and a potential tumor suppressor that binds to the adenoviral oncoprotein E1A. We show that the C-terminal Mynd domain of BS69 (amino acids 516-561) or the closely related Mynd domains of the Caenorhabditis elegans proteins Bra-1 and Bra-2 bind not only to E1A but also to the Epstein-Barr virus EBNA2 oncoprotein and the Myc-related cellular protein MGA. Interaction depends on intact PXLXP motifs present in all three proteins. Moreover, viral proteins compete for binding of BS69 to MGA in a PXLXP-dependent fashion. Because deletions in E1A or EBNA2 that cover the PXLXP motifs are non-transforming, our observations suggest a role for BS69 in cell growth control that is reminiscent of abrogation of the Rb function by various oncoproteins.